title: Glutamine contributes to ameliorate inflammation after renal ischemia/reperfusion injury in rats.
abstract: The aim of this study was to investigate the effects of glutamine in an in vivo rat model of renal ischemia/reperfusion (I/R) injury. Male Wistar rats underwent bilateral renal pedicle clamping for 45 min followed by reperfusion for 6 h. Glutamine (1.5 mg/kg) was administered intraperitoneally (i.p.) 15 min prior to reperfusion. Plasma concentrations of urea, creatinine, γ-glutamyl transferase (γ-GT), and aspartate aminotransferase (AST) were measured for the assessment of renal function and reperfusion injury. Markers of oxidative stress, expression of the pro-inflammatory mediators inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), AT-1 expression, and changes in the oxidative stress-sensitive nuclear factor kappa B (NF-κB) signaling pathway were measured to investigate whether glutamine can reduce the renal dysfunction. Kidney myeloperoxidase (MPO) activity and malondialdehyde (MDA) levels were measured for assessment of polymorphonuclear (PMN) cell infiltration and lipid peroxidation, respectively. Renal sections were used for histologic grading of renal injury and for immunohistochemical localization of nitrotyrosine and poly(ADP-ribose) synthetase (PARS). In vivo, glutamine significantly reduced the increase in urea, creatinine, γ-GT, AST, produced by renal ischemia/reperfusion (I/R), suggesting an improvement in both renal function and injury. Glutamine significantly reduced iNOS and NF-κB, kidney MPO activity and MDA levels, indicating a reduction in PMN infiltration and lipid peroxidation, respectively. Glutamine reduced the histological evidence of renal damage associated with I/R and caused a substantial reduction in the staining for nitrotyrosine and PARS, suggesting reduced nitrosative and oxidative stress. Moreover, glutamine attenuated the reduction of COX-2 expression and prevented the increased AT-1 expression after I/R. Our results suggest that glutamine reduces the renal dysfunction and injury associated with I/R of the kidney.
authors.affiliation: Istituto Di Ricovero e Cura a Carattere Scientifico (IRCCS) Centro Neurolesi Bonino-Pulejo, Messina, Italy.
authors.forename: Emanuela
authors.initials: E
authors.lastname: Esposito
authors.forename: Stefania
authors.initials: S
authors.lastname: Mondello
authors.forename: Rosanna
authors.initials: R
authors.lastname: Di Paola
authors.forename: Emanuela
authors.initials: E
authors.lastname: Mazzon
authors.forename: Domenico
authors.initials: D
authors.lastname: Italiano
authors.forename: Irene
authors.initials: I
authors.lastname: Paterniti
authors.forename: Patrizia
authors.initials: P
authors.lastname: Mondello
authors.forename: Carmela
authors.initials: C
authors.lastname: Aloisi
authors.forename: Salvatore
authors.initials: S
authors.lastname: Cuzzocrea
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D004195:Disease Models, Animal; D005973:Glutamine / Q000008:administration & dosage / Q000627:therapeutic use*; D007150:Immunohistochemistry; D007668:Kidney / Q000098:blood supply* / Q000201:enzymology / Q000276:immunology / Q000473:pathology; D007677:Kidney Function Tests; D008297:Male; D009393:Nephritis / Q000201:enzymology / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000201:enzymology / Q000276:immunology / Q000473:pathology
chemical_list: D005973:Glutamine